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Objective: To investigate purine metabolism in patients with systemic lupus erythematosus (SLE) for possible abnormalities that might be related to their overall impaired immune function., Methods: This pilot study included 17 patients with SLE (2 men, 15 women). Enzyme activities of the purine enzymes 5'-nucleotidase (5'NT), purine nucleoside phosphorylase (PNP), and hypoxanthine-guanine-phosphoribosyltransferase (HGPRT) were measured in peripheral blood mononuclear cells (PBMC) and also in fractions of T cells (differentiation antigen CD3+) (n = 12) and B cells (CD19+) (n = 9). The activity of the thiopurine enzyme thiopurine-methyltransferase (TPMT) was measured in red cell lysate. Routine blood tests and indices of disease activity were measured as well. Results were compared with those of healthy volunteers., Results: Compared with their controls, the female SLE patients had a more than 50% reduced activity of 5'NT in the T cell fraction (p = 0.001) and in PBMC (p < 0.000). 5'NT activity was also lower in B cells, but this was not statistically significant. Enzyme activities did not correlate with indices of disease activity, disease duration or the B cell/T cell ratio and no influence of medication was found., Conclusion: Reduced lymphocyte 5'NT activity is a novel finding in SLE. These results indicate that purine metabolism in SLE may be disturbed. Consequences of a low 5'NT activity may be an intracellular accumulation of (deoxy)purine nucleotides and a reduction of adenosine production. It is hypothesised that these factors may play a part in the overall impaired immune function and in the chronicity of inflammation in SLE.

Objective: Purine enzyme activities may predict the effectiveness of azathioprine treatment and be associated with increased deaths from infectious diseases. In rheumatoid arthritis, patients show variable responses to azathioprine and a higher percentage of death is caused by infections. The aim of the study was to investigate possible rheumatoid arthritis associated abnormalities of purine enzyme activities by measuring several of these enzymes in patients with recent onset rheumatoid arthritis before treatment with disease modifying antirheumatic drugs or prednisone., Methods: 23 patients with recent onset rheumatoid arthritis and 28 healthy controls were studied. Activities of the enzymes 5'-nucleotidase, purine nucleoside phosphorylase (PNP), hypoxanthine guanine phosphoribosyltransferase (HGPRT), and thiopurine methyltransferase (TPMT) were measured. Assessment of disease activity and blood sampling for routine measurements and HLA typing were done simultaneously., Results: Purine enzyme activities did not differ between patients and healthy controls. Enzyme activities had no significant relations with indices of disease activity or rheumatoid factor titre or with the rheumatoid arthritis associated HLA types. Activity of 5'nucleotidase decreased with age (P < or = 0.05) and was lower by about 27% (P = 0.007) in males than in females., Conclusions: In rheumatoid arthritis patients, neither the variability in azathioprine effectiveness nor the increased death rate from infections can be explained by pre-existing abnormalities in the activities of the purine enzymes 5'-nucleotidase, PNP, HGPRT, or TPMT at an early stage of the disease, before disease modifying antirheumatic drugs or prednisone treatment. Besides adjustment for age, results of studies involving purine 5' nucleotidase activity should also be adjusted for sex.

Objective: To study the possible association of purine enzyme activities with response to azathioprine (AZA) treatment in rheumatoid arthritis (RA) and their correlation with parameters of disease activity., Patients and Methods: Lymphocyte activities of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT), adenine phosphoribosyltransferase (APRT), purine nucleoside phosphorylase (PNP) and 5'-nucleotidase (5NT), and erythrocyte activities of thiopurine methyltransferase (TPMT) were measured in 14 healthy controls and 36 patients with RA. Eight patients had not previously been treated with AZA. Response to AZA therapy in 28 patients, determined in a prospective trial, was considered good in nine (group 1), insufficient in seven (group 2). In 12 patients AZA was withdrawn because of adverse reactions (group 3). Disease activity parameters were obtained simultaneously with purine enzyme measurements. Purine enzyme levels in the different groups were compared., Results: Levels of 5NT activity were significantly lower in patients with RA than in healthy controls. PNP activity was higher in patients with RA not using prednisone compared with those who did and healthy controls. No clear correlation between purine enzyme levels and disease activity parameters was found. 5NT activities were significantly higher in group one than in group three (p = 0.012; alpha = 0.017), and almost significantly higher than in group two (p = 0.03; alpha = 0.017)., Conclusions: The results indicate that purine enzyme activities in patients with RA differ from healthy controls, are associated with the outcome of AZA treatment and seem not to be associated with disease activity. Our findings may offer a clue to predict the response to AZA therapy in RA.